Use of nanodispersions in cosmetic end formulations

ABSTRACT

A description is given of the use of a nanodispersion, which comprises
     (a) a membrane-forming molecule,   (b) a coemulsifier and   (c) a lipophilic component,   in cosmetic end formulation, which nanodispersion is obtainable by   (α) mixing the components (a), (b) and (c) until a homogeneous clear liquid is obtained, and   (β) adding the liquid obtained in step (α) to the water phase of the cosmetic end formulations, steps (α) and (β) being carried out without any additional supply of energy.   

     The nanodispersions used according to this invention can be easily prepared and are suitable as carrier systems for a very wide range of cosmetic active agents and oil-soluble dyes.

This is a continuation of application Ser. No. 09/306,005, filed on May6, 1999 now abandoned.

The present invention relates to the use of specific nanodispersions incosmetic end formulations, to cosmetic end formulations comprising saidnanodispersions and to the different cosmetic uses of these endformulations.

Cosmetic preparations comprising, in addition to the basic substancesresponsible for forming the cosmetic formulations, other functionalactive agents. These are added to the cosmetic base formulations and areused, for example, for treatment, protection, colouring, cleansing,disinfection, for moisturising skin and for regenerating and activatingskin or hair.

In order for these substances to have an effect at the desired site,they must be transported to the respective site, for example to the skinsurface, mucosae, nails, dental enamel or hair, but also to theepidermal and dermal areas of the skin, by means of so-called carrierand transport vehicles (carrier systems). To this purpose, many cosmeticactive agents, for example water-soluble vitamins, the amino acid groupor the water-soluble melanines, are encapsulated in liposomes. Owing tothe properties of the liposomes, lipophilic substances can beencapsulated only in minor amounts in the lipophilic areas of theliposome membrane. For this reason, so-called nanoemulsions, also callednanoparticles, are used for such compounds, e.g. fat-soluble vitamins.

Owing to the physical and chemical properties of the membranes and themembrane-forming molecules, the use of said carrier systems inconventional cosmetic formulations is severely limited.

Conventionally structured membranes are highly susceptible toamphiphilic substances, such as ionogenic or non-ionogenic emulsifiers,fatty amines, amphoteric emulsifiers, detergent surfactants, thickenersor preservatives which form the basis for many cosmetic preparations orwhich are present as so-called active agents or excipients in cosmeticend formulations. The structure of the membranes changes in the presenceof such substances, which may result in the destruction of the addedcarrier system during preparation.

Customary membranes are also exposed to the attack of acids and bases.Thus, it is required, for example, that carrier systems containingphospholipids can only be used in the range of the so-called pH optimumof about pH 6.5. Lowering or raising of the pH results in the hydrolysisof the membrane-forming molecules.

Surprisingly, it has now been found that nanodispersions of suitablecomposition can, in the presence of amphiphilic substances, beincorporated into cosmetic end formulations over a wide pH range in verysimple manner while retaining their morphological and physicochemicalproperties.

Accordingly, this invention relates to the use of a nanodispersion,which comprises

-   (a) a membrane-forming molecule,-   (b) a coemulsifier and-   (c) a lipophilic component,    in cosmetic end formulations, the nanodispersion being obtainable by-   (α) mixing the components (a), (b) and (c) until a homogeneous clear    liquid is obtained (so-called nanodispersion prephase), and-   (β) adding the liquid obtained in step (α) to the water phase of the    cosmetic end formulations, wherein steps (α) and (β)are carried out    without any additional supply of energy.

Step (α) is usually carried out at room temperature, where necessarywith heating and under normal pressure conditions. Mixing is carried outusing standard stirring apparatus, for example propeller, angled paddleor magnetic agitators, and without using any special mechanical stirringaids.

Components (a), (b) and (c) (=step (α)) are mixed in anhydrous medium,i.e. it is not necessary to add any water.

Step (β) is carried out by adding the liquid obtained in step (α), thenanodispersion pre-phase, to the water phase of the cosmetic endformulations. The particular choice of components (a), (b) and (c)results directly in ultrafine, monodisperse nanodispersions. In thiscase it is possible to forego homogenisation via nozzle, rotor-stator orultrasound homogenisers, which is usually carried out to convertcoarsely disperse or at least heterodisperse systems to finemonodisperse systems. Step (β) is thus characterised by the absence ofhigh shear or cavitation forces.

Step (β) is usually carried out at room temperature, which is the rangeof the respective oil/water phase inversion temperature (PIT).

The nanodispersions characterised by the process steps (α) and (β)contain particles having an average diameter of <50 nm, typically ofless than 30 nm. The distribution is monodisperse and correspons to aGaussian distribution.

According to this invention, it is preferred to use a nanodispersionwhich contains,

-   (a) as membrane-forming molecules, substances which are suitable for    forming so-called bilayers,-   (b) as coemulsifiers, substances which preferably form O/W    structures and,-   (c) as lipophilic component, a functional lipophilic active agent    customarily used in cosmetics.

The nanodispersion preferably contains as component (a) a phospholipid,a hydrated or partially hydrated phospholipid, a lysophospholipid, aceramide, or mixtures of these compounds.

A very particularly preferred phospholipid is that of formula

wherein

-   R₁ is C₁₀-C₂₀acyl;-   R₂ is hydrogen or C₁₀-C₂₀acyl-   R₃ is hydrogen, 2-trimethylamino-1-ethyl, 2-amino-1-ethyl;    C₁-C₅alkyl which is unsubstituted or substituted by one or several    carboxy, hydroxy or amino groups; the inositol or glyceryl group;-   or salts of these compounds.

C₁₀-C₂₀Acyl is preferably straight-chain C₁₀-C₂₀alkanoyl containing aneven number of carbon atoms and straight-chain C₁₀-C₂₀alkenoylcontaining a double bond and an even number of carbon atoms.

Straight-chain C₁₀-C₂₀alkanoyl containing an even number of carbon atomsis, for example, n-dodecanoyl, n-tetradecanoyl, n-hexadecanoyl orn-octadecanoyl.

Straight-chain C₁₀-C₂₀alkenoyl containing a double bond and an evennumber of carbon atoms is, for example, 6-cis- or 6-trans-, 9-cis- or9-trans-dodecenoyl, -tetradecenoyl, -hexadecenoyl, -octadecenoyl or-eicosenoyl, preferably 9-cis-octa-decenoyl (oleoyl), and also9,12-cis-octadecadienoyl or 9,12,15-cis-octadecatrienoyl.

A phospholipid of formula (1), wherein R₃ is 2-trimethylamino-1-ethyl,is referred to by the trivial name lecithin, and a phospholipid offormula (1), wherein R₃ is 2-amino-1-ethyl, by the trivial namecephalin. Suitable are, for example, naturally occurring cephalin orlecithin, e.g. cephalin or lecithin from soybeans or chicken eggs withdifferent or identical acyl groups, or mixtures thereof.

The phospholipid of formula (1) may also be of synthetic origin. Theexpression “synthetic phospholipid” is used to define phospholipidshaving uniform composition with respect to R₁ and R₂. Such syntheticphospholipids are preferably the lecithins and cephalins defined above,wherein the acyl groups R₁ and R₂ have a defined structure and which arederived from a defined fatty acid having a degree of purity greater thanabout 95%. R₁ and R₂ may be identical or different and unsaturated orsaturated. Preferably, R₁ is saturated, for example n-hexadecanoyl, andR₂ is unsaturated, for example 9-cis-octadecenoyl (oleoyl).

The expression “naturally occurring” phospholipid defines a phospholipidthat does not have a uniform composition with respect to R₁ and R₂. Suchnatural phospholipids are likewise lecithins and cephalins, wherein theacyl groups R₁ and R₂ are derived from naturally occurring fatty acidmixtures.

The requirement “substantially pure” phospholipid of formula (1) definesa degree of purity of more than 90% by weight, preferably of more than95% by weight of the phospholipid of formula (1), which can bedemonstrated by means of suitable determination methods, for example bypaper chromatography, thin-layer chromatography, by HPLC or by means ofenzymatic colour testing.

In a phospholipid of formula (1), R₃ defined as C₁-C₄alkyl is, forexample, methyl or ethyl. Methyl is preferred.

R₃ defined as C₁-C₅alkyl substituted by one or several carboxy, hydroxyor amino groups is, for example, 2-hydroxyethyl, 2,3-dihydroxy-n-propyl,carboxymethyl, 1- or 2-carboxyethyl, dicarboxymethyl,2-carboxy-2-hydroxyethyl or 3-carboxy-2,3-dihydroxy-n-propyl,3-amino-3-carboxy-n-propyl or 2-amino-2-carboxy-n-propyl, preferably2-amino-2-carboxyethyl.

Phospholipids of formula (1) containing these groups can be present insalt form, for example as sodium or potassium salt.

Phospholipids of formula (1), wherein R₃ is the inositol or glycerylgroup, are known by the names phosphatidylinositol andphosphatidylglycerol.

The acyl radicals in the phospholipids of formula (1) are alsocustomarily known by the names given in brackets:

-   9-cis-dodecenoyl (lauroleoyl), 9-cis-tetradecenoyl (myristoleoyl),    9-cis-hexadecenoyl (palmitoleoyl), 6-cis-octadecenoyl (petroseloyl),    6-trans-octadecenoyl (petroselaidoyl), 9-cis-octadecenoyl (oleoyl),    9-trans-octadecenoyl (elaidoyl), 9,12-cis-octadecadienoyl    (linoleoyl), 9,12,15-cis-octadecatrienoyl (linolenoyl),    11-cis-octadecenoyl (vaccenoyl), 9-cis-eicosenoyl (gadoleoyl),    5,8,11,14-cis-eicosatetraenoyl (arachidonoyl), n-dodecanoyl    (lauroyl), n-tetradecanoyl (myristoyl), n-hexadecanoyl (palmitoyl),    n-octadecanoyl (stearoyl), n-eicosanoyl (arachidoyl), n-docosanoyl    (behenoyl), n-tetracosanoyl (lignoceroyl).

A salt of the phospholipid of formula (1) is preferably cosmeticallyacceptable. Salts are defined by the existence of salt-forming groups inthe substituent R₃ and by the free hydroxyl group at the phosphorusatom. The formation of internal salts is also possible. Alkali metalsalts, especially the sodium salt, are preferred.

In a particularly preferred embodiment of this invention, purifiedlecithin from soybeans of the quality LIPOID S 100 or S 75, or alecithin defined in the monograph USP23/NF 18, is used.

Component (a) is preferably used in a concentration of about 0.1 to 30%by weight, based on the total weight of the components (a), (b) and (c).

Component (b) is preferably an emulsifier or emulsifier mixtures formingthe preferred O/W structures.

Especially preferred emulsifiers are

-   -   alkali, ammonium and amine salts of fatty acids. Examples of        such salts are the lithium, sodium, potassium, ammonium,        triethylamine, ethanolamine, diethanolamine or triethanolamine        salts. It is preferred to use the sodium, potassium or ammonium        (NR1R2R3) salts, wherein R₁, R₁ and R₁ are each independently of        one another hydrogen, C₁-C₄alkyl or C₁-C₄hydroxyalkyl.    -   saturated and unsaturated alkyl sulfates, such as sodium        docecylsulfate and alkanesulfonates such as sodium        dodecanesulfonate;    -   salts of colic acid, such as sodium cholate, sodium glycocholate        and sodium taurocholate;    -   invert soaps (quats), such as zetylpyridinium chloride;    -   partial fatty acid esters of sorbitan, such as sorbitan        monolaurate;    -   sugar esters of fatty acids, such as sucrose monolaurate;    -   alkylglucosides, such as n-octylglucoside or n-dodecylglucoside;    -   alkylmaltosides, such as n-dodecylmaltoside;    -   fatty acid partial glycerides, such as lauric acid        monoglyceride;    -   C₈-C₁₈betaines, C₈-C₂₄alkylamido-C₁-C₄alkylenebetaines and        C₈-C₁₈sulfobetaines;    -   proteins, such as casein;    -   polyglycerol esters of fatty acids;    -   propylene glycol esters of fatty acids;    -   lactates of fatty acids, such as sodium        stearoyllactyl-2-lactate;    -   fatty alcohol phosphorates.

Emulsifiers of the polyoxyethylene type are very particularly preferred.Examples of such emulsifiers are:

-   -   polyethoxylated sorbitan fatty acid esters, such as polysorbate        80;    -   polyethoxylated fatty alcohols, such as oleth-20;    -   polyethoxylated fatty acids, such as polyoxyl 20 stearate;    -   polyethoxylated vitamin E derivatives, such as vitamin E        polyethylene glycol 1000 succinate;    -   polyethoxylated lanoline and lanoline derivatives, such as        laneth-20;    -   polyethoxylated fatty acid partial glycerides, such as        diethylene glycol monostearate;    -   polyethoxylated alkylphenols, such as ethylphenolpoly(ethylene        glycol ether)11;    -   sulfuric acid semiester polyethoxylated fatty alcohols and their        salts, such as C₁₂-C₁₄-fatty alcohol ether sulfate-2 EO-sodium        salt;    -   polyethoxylated fatty amines and fatty acid amides;    -   polyethoxylated carbon hydrates    -   block polymers of ethylene oxide and propylene oxide, such as        poloxamer 188.

The nanodispersion preferably contains as component (b) at least oneemulsifier of the polyoxyethylene type, and very particularly preferablyan emulsifier of the polyoxyethylene type, or a mixture of thesesubstances.

Component (b) is present in the nanodispersion used according to thisinvention in a concentration of about 1 to about 50% by weight, based onthe total weight of components (a), (b) and (c).

Component (c) is preferably a natural or synthetic or a partiallysynthetic di- or triglyceride, a mineral oil, silicone oil, wax, fattyalcohol, guerbet alcohol or the ester thereof, a lipophilic functionalcosmetic active agent including sunscreens, or a mixture of thesesubstances.

Component (c) is particularly preferably a sunscreen or a fat-solublevitamin.

An active agent, active agent composition or active agent extractsuitable for skin cosmetics is an ingredient or a mixture of ingredientswhich is approved for dermal or topic administration.

Examples to be listed are:

-   -   active agents which have cleansing action on the skin surface        and hair. These include all those substances which are used for        cleansing the skin, for example oils, soaps, syndets and solid        substances;    -   active agents having a deodorising and antiperspirant action:        these include antiperspirants based on aluminium or zinc salts,        deodorants containing bactericidal or bacteriostatic deodorising        substances, for example triclosan, hexachlorophene, alcohols and        cationic substances, for example quaternary ammonium salts and        smell absorbers, for example ®Grillocin (combination of zinc        rizinoleate and different additives) or triethylcitrates,        optionally in combination with an antioxidant, such as        butylhydroxytoluene), or ion exchange resins;    -   active agents offering protection against sunlight (UV filters):        suitable active agents are filter substances (sunscreens) which        can absorb the UV radiation from sunlight and convert it into        heat. Depending on the desired effect, the following sunscreens        are preferred: sunscreens which selectively absorb energy-rich,        sunburning UV radiation in the range from about 280 to 315 nm        (UV-B absorbers) and which transmit the longwave range from        about 315 to 400 nm (UV-A range), and sunscreens which only        absorb the longwave radiation of the UV-A range from 315 to 400        nm (UV-A absorbers).

Suitable sunscreens are, for example, organic UV absorbers from theclass of the p-aminobenzoic acid derivatives, salicylic acidderivatives, benzophenone derivatives, dibenzoylmethane derivatives,diphenylacrylate derivatives, benzofuran derivatives, polymeric UVabsorbers containing one or more than one silicium-organic radical,cinnamic acid derivatives, camphor derivatives, trianilino-s-triazinederivatives, phenylbenzimidazolesulfonic acid and the salts thereof,menthylanthranilates, benzotriazole derivatives, and/or an inorganicmicropigment selected from the group consisting of TiO₂, zinc oxide ormica encapsulated with aluminium oxide or silicium dioxide.

Examples of p-aminobenzoic acid derivative compounds are:

4-aminobenzoic acid (PABA); ethyidihydroxypropyl-PABA of formula

wherein m, n and x have the same meaning and each is at most 25;

octyldimethyl PABA of formula

Examples of salicylic acid derivative compounds are:

Homomenthylsalicylate of formula

Examples of benzophenone derivative compounds are:

-   benzophenone-3-(2-hydroxy-4-methoxybenzophenone),    benzophenone-4-(2-hydroxy-4-methoxybenzophenone-5-sulfonic acid) or    benzophenone-8-(2,2′-dihydroxy-4-methoxybenzophenone).

Examples of dibenzoylmethane derivative compounds are:

-   butylmethoxydibenzoylmethane-[1-(4-tert-butyl)-3-(4-methoxyphenyl)propane-1,3-dione].

Examples of diphenylacrylate derivative compounds are:

-   octocrylene(2-ethylhexyl-2-cyano-3,3′-diphenylacrylate) or    etocrylene(ethyl-2-cyano-3,3′-diphenylacrylate).

Examples of benzofuran derivative compounds are:

-   3-(benzofuranyl)-2-cyanoacrylate,    2-(2-benzofuranyl)-5-tert-butylbenzoxazole or    2-(p-aminophenyl)benzofuran and, in particular, the compound of    formula

Examples of polymeric UV absorber compounds containing one or more thanone silicium-organic radical are:

benzylidenemalonate derivatives, in particular the compound of formula

wherein

-   R₂₄ is hydrogen or O—Me, and-   r is approximately 7; the compound of formula

Examples of cinnamate compounds are:

-   octylmethoxycinnamate (4-methoxycinnamic acid-2-ethylhexyl ester),    diethanolaminemethoxycinnamate (diethanolamine salt of    4-methoxycinnamic acid), isoamyl-p-methoxycinnamate    (4-ethoxycinnamic acid-2-isoamyl ester),    2,5-diisopropylmethylcinnamate or a cinnamic acid amido derivative.

Examples of camphor derivative compounds are:

-   4-methylbenzylidene camphor [3-(4′-methyl)benzylidenebornan-2-one],    3-benzylidenecamphor (3-benzylidenebornan-2-one),    polyacrylamidomethylbenzylidenecamphor {N-[2(and    4)-2-oxyborn-3-ylidenemethyl)benzyl]acrylamide polymer},    trimoniumbenzylidenecamphorsulfate-[3-(4′-trimethylammonium)benzylidenebornan-2-onemethylsulfate],    terephthalydenedicamphorsulfonic acid    {3,3′-(1,4-phenylenedimethine)-bis-(7,7-dimethyl-2-oxobicyclo-[2.2.1]heptane-1-methanesulfonic    acid} or the salts thereof, or benzylidenecamphorsulfonic acid    [3-(4′-sulfo)benzylidenebornan-2-one] or the salts thereof.

Examples of trianilino-s-triazine derivative compounds are:

-   octyltriazine-[2,4,6-trianilino-(p-carbo-2′-ethyl-1′-oxy)-1,3,5-triazine    and the trianilino-s-triazine derivatives described in U.S. Pat. No.    5,332,568, U.S. Pat. No. 5,252,323, WO 93/17002 and WO 97/03642 and    EP-A-0,517,104; the resorcinyltriazines described in EP-A-0,775,698,    in particular the compounds of formula

Examples of benzotriazole compounds are:

-   2-(2-hydroxy-5-methylphenyl)benzotriazole; the benzotriazole    compounds disclosed in EP-A-0,746,305, in particular the compound of    formula    wherein T₂ is hydrogen; or C₁-C₈alkyl;    -   insect repellents: repellents are compositions which should        prevent insects from touching the skin and getting active there.        They repel the insects and slowly evaporate. The most frequently        used repellent is dethyltoluamide (DEET). Other customary        repellents are to be found in “W. Raab and U. Kindl,        “Pflegekosmetik”, Gustav-Fischer-Verlag Stuttgart/New York,        1991, p. 161;    -   active agents protecting against chemical and mechanical attack:        these include all those substances which form a barrier between        the skin and the outer noxa, such as paraffin oils, silicone        oils, vegetable oils, PCL products and lanoline as protection        against aqueous solutions, film formers, such as sodium        alginate, triethanolamine alginate, polyacrylates, polyvinyl        alcohol or cellulose ethers against the action of organic        solvents, or substances based on mineral oils, vegetable oils or        silicone oils as “lubricants” against high mechanical stresses        of the skin;    -   moisturising substances: the following substances are used as        moisturisers: sodium lactate, urea, alcohols, sorbitol,        glycerol, propylene glycol, collagen, elastin or hyaluronic        acid;    -   active agents having ceratoplastic activity: benzoylperoxide,        retinic acid, colloidal sulfur and resorcinol;    -   antimicrobial agents, for example triclosan or quaternary        ammonium compounds;    -   dermally applicable oily or oil-soluble vitamins or vitamin        derivatives: e.g. vitamin A (getinol in the form of the free        acid or its derivatives), panthenol, pantothenic acid, folic        acid, and combinations thereof, vitamin E (tocopherol), F;        essential fatty acids; or niacin-amide (nicotinic acid amide);    -   vitamin-based placenta extracts: active agent compositions        mainly with vitamin A, C, E, B₂₁ B₁₂, folic acid and biotin,        amino acids and enzymes and also compounds of the trace elements        magnesium, silicium, phosphorus, calcium, manganese, iron or        copper.    -   skin repair complexes: obtainable from inactivated and        desintegrated cultures of bacteria of the bifidus group;    -   plants and plant extracts: for example arnica, aloe, beard        lichen, ivy, nettle, ginseng, henna, camomile, calendula,        rosemary, sage, equisetum or thyme;    -   animal extracts: for example royal jelly, propolis, proteins or        thymus extracts;    -   dermally applicable cosmetic oils: neutral oils of the miglyol        812 type, apricot kernel oil, avocado oil, babassu oil,        cottonseed oil, borage oil, thistle oil, groundnut oil,        gamma-oryzanol, rosehip seed oil, hemp oil, hazelnut oil,        currant seed oil, jojoba oil, cherrystone oil, salmon oil,        linseed oil, corn oil, macadamia nut oil, almond oil, evening        primrose oil, mink oil, olive oil, pecan nut oil, peach kernel        oil, pistachio nut oil, rapeseed oil, rice germ oil, castor oil,        safflower oil, sesame oil, soybean oil, sunflower oil, tea tree        oil, grapeseed oil or wheat germ oil.

Component (c) is present in the nanodispersions used according to thisinvention in a concentration of preferably 0.1 to 80% by weight, basedon the total weight of components (a), (b) and (c).

Components (a), (b) and (c) can be present in the nanodispersions usedaccording to this invention as individual compounds or as mixtures ofseveral different individual components.

At least one component (a), (b) or (c) in the nanodispersion compositionis usually a functional active agent used in cosmetics for treating orprotecting the skin, mucosae and hair.

The nanodispersion used according to this invention optionally comprisesas facultative component (d) a solubilising agent, preferably aC₂-C₈alcohol, such as ethanol or propylene glycol.

A nanodispersion containing the components (a), (b), (c) and optionally(d) is distinguished by favourable phase properties of the solubilisedfunctional cosmetic agent. Thus if there is opalescence and transparencyin incident light, only a very slight turbidity shows that thedispersion is physically still different from the ideal state of agenuine molecular solution. Electron microscopic images show that apopulation of more than 98% is present in a Gaussian distribution as asuspension of particles (nanoparticles) having a particle size of lessthan about 50 nm, typically of less than about 30 nm. However, thesedistinctions from a genuine solution can be tolerated because of theparticularly good homogeneity properties of the dispersion which can beevidenced, for example, by a surprisingly high storage stability, e.g.no separation after storing for several months at temperatures of up toroom temperature (stability to be expected by extrapolation: more thantwo years).

Laser light scattering measurements and electron microscopic analysis(Cryo-TEM) confirm the very small size and excellent homogeneity of thenanoparticles present in the nanodispersion.

Another advantage of the nanodispersions used according to thisinvention is that they are easy to prepare.

The nanodispersions characterised by claim 1 are used according to thisinvention for cosmetic end formulations.

This invention also relates to the so-called nanodispersion prephasecharacterised in step (α), which is obtainable by mixing the components

-   (a) membrane-forming molecules,-   (b) coemulsifier,-   (c) lipophilic component and, optionally,-   (d) a C₂-C₈alcohol, preferably propylene glycol and, more    preferably, ethanol until a homogeneous clear liquid is obtained,    mixing being carried out in anhydrous medium.

These nanodispersion prephases can likewise be directly used inaccordance with this invention for cosmetic end formulations.

Cosmetic end formulations include a very wide range of cosmeticproducts. Suitable products are, for example, especially the following:

-   -   skin-care products, for example skin washing and cleansing        products in the form of bars of soap or liquid soaps, syndets or        washing pastes,    -   bath products, for example liquid (foam baths, milks, shower        products) or solid bath products, such as bath pearls and bath        salts;    -   skin-care products, such as skin emulsions, multiple emulsions        or skin oils;    -   decorative body-care products, for example face make-ups in the        form of day or powder creams, face powders (lose and        compressed), rouge or cream make-ups, eye-care products, for        example eye shadow products, mascara, eyeliners, eye creams or        eye-fix creams; lip-care products, for example lipstick, lip        gloss, lip liner, nail-care products, such as nail varnish, nail        varnish remover, nail hardeners or cuticle removers;    -   feminine hygiene products, such as feminine hygiene washing        lotions or sprays;    -   foot-care products, for example foot baths, foot powders, food        creams or foot balms, special deodorants and antiperspirants or        products for scrubbing off callouses;    -   sunscreens, such as sun milks, lotions, creams, oils,        sunblockers or tropicals, pre-sun products or after-sun        products;    -   suntanning products, for example self-tanning creams;    -   depigmenting products, for example products for bleaching or        lightening skin;    -   insect repellents, for example insect oils, lotions, sprays or        sticks;    -   deodorants, for example deodorant sprays, non-aerosol sprays,        deodorant gels, sticks or roll-ons;    -   antiperspirants, for example antiperspirant sticks, creams or        roll-ons;    -   products for cleansing and treating impure skin, for example        syndets (solid or liquid), peeling or scrubbing products or        peeling masks;    -   chemical depilatory products, for example depilatory powders,        liquid depilatory products, creamy or pasty depilatory products,        depilatory gels or aerosol foams;    -   shaving products, for example shaving soap, foaming shaving        creams, non-foaming shaving creams, shaving foams and gels,        preshaving products for dry shaving, aftershaves or aftershave        lotions;    -   scents, for example perfumes (Eau de Cologne, Eau de Toilette,        Eau de Parfum, Parfum de Toilette, perfume), perfume oils or        perfume creams;    -   products for oral and dental hygiene as well as for dentures,        for example toothpastes, tooth gels, tooth powders, mouth-wash        concentrates, anti-plaque mouth-washes, denture cleaning        products or denture adhesion products;    -   cosmetic formulations for hair treatment, for example hair        washes in the form of shampoos, hair conditioners, hair-care        products, for example pretreatment products, hair tonics, hair        styling creams and gels, pomades, hair rinses, deep conditioning        treatments, intensive hair care treatments, hair setting        products, for example waving agents for perms (hot wave, mild        wave, cold wave), hair straightening products, liquid hair        fixatives, hair foams, hair sprays, bleaching agents, for        example hydrogen peroxide solutions, bleaching shampoos,        bleaching creams, bleaching powders, bleaching pastes or oils,        temporary, semitemporary or permanent hair dyes, products        containing self-oxidising dyes, or natural hair dyes, such as        henna or camomile.

The end formulations listed above can be in a very wide range of formsof presentation, for example

-   -   in the form of liquid formulations as an O/W emulsion,    -   in the form of a gel,    -   in the form of an oil, cream, milk or lotion,    -   in the form of a powder, lacquer, pellets or make-up,    -   in the form of a stick,    -   in the form of a spray (spray with propellant or non-aerosol        spray) or an aerosol,    -   in the form of a foam, or    -   in the form of a paste.

The liquid and semisolid forms of presentation in this case contain thenanodispersion with the components (a), (b) and (c) in the aqueousphase, and one or several of the above functional cosmetic activeagent(s). Solid forms of presentation contain the nanodispersion in thedehydrated form, the dehydration of the nanodispersion usually beingcarried out by freeze-drying or spray-drying in the presence ofcustomary auxiliaries. For some end formulations it is advantageous toreplace the nanodispersion with the corresponding nanodispersionsprephase.

Emulsions are heterogeneous systems consisting of two liquids (phases)which are not, or only partly, miscible with each other. One phase ispresent in the form of droplets (dispersed or inner phase), whereas theother forms a continuous phase as a liquid. In the case of an O/Wemulsion, which is basically characterised by water, oil droplets arefinely dispersed in water.

Creams are usually spreadable in the temperature range from room to skintemperature, whereas lotions or milks tend to be pourable.

Gels are semisolid, more or less transparent systems in which theso-called gel former forms a three-dimensional network in which a liquidis immobilised. The clear to opaque hydrogels consist primarily ofwater, water-soluble substances and thickeners or gel formers. If lipidsare additionally incorporated, the slightly creamy-lookinghydrodispersion gels are obtained. In contrast, the oleogels are free ofwater and contain lipids as liquid components.

The cosmetic end formulation containing one or several of the aboveingredients which may be in the form of the above-mentioned forms ofpresentation, contains the nanodispersion used according to thisinvention preferably in a concentration of 0.01 to 100, preferably of0.01 to 20.0, more preferably of 0.05 to 5% by weight.

These end formulations are another subject matter of this invention.

The end formulations in this case contain the nanodispersion in theiraqueous phase in a concentration of 0.01 to 20.0, preferably of 0.05 to10 and, more preferably of 0.1 to 5% by weight.

The end formulation used according to this invention can also containother components, for example emollients, emulsion stabilisers, skinmoisturisers, suntanning accelerators, thickeners, such as xanthane,moisture retention agents, such as glycerol, preservatives, such asparabene, antioxidants, as well as fragrances and colourants.

The basic formulations for the cosmetic end formulations according toExamples 14 to 21 are prepared in accordance with the instructions in“Kosmetik; Entwicklung, Herstellung und Anwendung kosmetischer Mittel”(Ed.: W. Umbach, Georg Thieme Verlag Stuttgart, New York) and with thedocumentations from “DGK Fortbildungskurs 1998, Entwicklung modernerHautpflegemittel”.

The end formulations are prepared by the customary known methods, someof which are described in the above literature. In the case of liquidand semisolid end formulations, the nanodispersions are alwaysincorporated into the aqueous phase of the end formulations. To thispurpose, they are taken up in a small proportion of the aqueous phaseand are added, as active agent phase, as last phase during thepreparation of a formulation at about 20 to 30° C. It is also possibleto add instead of the nanodispersion the corresponding nanodispersionprephase to the water phase of the end formulation. He nanodispersionprephase is added to the water phase with stirring and preferably at atemperature in the range of the respective oil/water phase inversiontemperature (PIT).

In the case of solid end formulations it is advantageous to admix thedehydrated form of the nanodispersion to the solid substance mixture.

The cosmetic end formulation is preferably used for the treatment andprotection of skin, mucosae or hair and, very particularly, as sunscreenor as an after-sun preparation.

The nanodispersions used according to this invention can also be used astransport vehicles for oil-soluble dyes.

In another of its aspects, this invention thus relates to the use of thenanodispersion defined in claim 1 as carrier system for oil-solubledyes.

Suitable dyes are of synthetic or also of natural origin and arecomposed from all known chromophores, for example azo, azoic,anthraquinone, caratenoid, quinoline, xanthene, diarylmethane,triarylmethane, stilbene, indigoid, phtalocyanine, nitro dyes as well asall other known chromophores, such as are also listed in Colour Indexunder CI 11000 to CI 77999.

Of these dyes, those are particularly interesting which are at leastpartially soluble in organic media such as oils. This includes, forexample, those dyes which are called solvent dyes or disperse dyes, thedisperse dyes also including the group of the unloaded, directlyabsorbing hair dyes, for example derivatives of nitrobenzene or ofnitrodiphenylamine.

Examples of solvent dyes which may be used in accordance with thisinvention are:

Solvent Black 3 (Cas-No.: 4197-25-5); Solvent Black 5 (Cas-No.:11099-03-9); Solvent Blue 35 (Cas-No.: 12769-17-4); Solvent Green 3;Solvent Green 7 (Cas-No.: 6358-69-6); Solvent Orange 1 (Cas-No.:2051-85-6); Solvent Red 24 (Cas-No.: 85-83-6); Solvent Red 43 (Cas-No.:15086-94-9); Solvent Red 48 (Cas-No.: 13473-26-2); Solvent Red 49:1(Cas-No.: 6373-07-5); Solvent Red 72 (Cas-No.: 596-03-2); Solvent Yellow44 (CAS No.: 2478-20-8); Solvent Yellow 18 (CAS No.: 6407-76-9).

Examples of disperse dyes which may be used in accordance with thisinvention are:

Disperse Black 9 (CAS No.: 12222-60-4); Disperse Blue 1 (CAS Nos.:2475-45-8); Disperse Blue 3 (CAS No.: 2475-46-9); Disperse Brown 1 (CASNo.: 23355-64-8); Disperse Orange 3 (CAS No.: 730-40-5); the compound offormula

Disperse Violet 1 (CAS-No.: 128-95-0); Disperse Violet 4(CAS-No.:1220-94-6); the compound of formula

examples of (unloaded) directly absorbing hair dyes are:

HC Blue No. 2 (CAS-No.: 33229-34-4); HC Blue No. 4 (reaction product ofN-methyl-1,4-diaminoanthraquino epichlorohydrin and monoethanolamine);HC Blue No. 5 (CAS-No.: 68478-64-8); the compound of formula

HC Blue No. 7 (Cas-No.: 90817-34-8); HC Blue No. 8 (Cas-No.:22366-99-0); HC Blue No. 9 (Cas-No.: 114087-42-2); HC Blue No. 10(Cas-No.: 102767-27-1); HC Blue No. 11 (Cas-No.: 23920-15-2); HC BlueNo. 12 (Cas-No.: 132885-85-9); the compound of formula

HC Blue No. 14 (Cas-No.: 99788-75-7); HC Orange No. 1 (Cas-No.:54381-08-7); HC Orange No. 2 (Cas-No.: 85765-48-6), HC Orange No. 3(Cas-No.:81612-54-6); the compound of formula

HC Red No. 1 (Cas-No.: 2784-89-6); HC Red No. 3 (Cas-No.: 2871-01-4); HCRed No. 7 (Cas-No.: 24905-87-1); HC Red No. 8 (Cas-No.: 13556-29-1); HCRed No. 9 (Cas-No.:56330-88-2); HC Red No. 10 (Cas-No.: 95576-89-9);, HCRed No. 11 (Cas-No.: 95576-92-4), HC Red No. 13 (Cas-No.: 94158-13-1);the compound of formula

HC Violet No. 1 (Cas-No.: 82576-75-8); the compound of formula

HC Yellow No. 2 (Cas-No.: 4926-55-0); HC Yellow No. 4 (Cas-No.:59820-43-8); HC Yellow No. 5 (Cas-No.: 56932-44-6); HC Yellow No. 6(Cas-No.: 104335-00-6); the compound of formula

HC Yellow No. 8 (Cas-No.: 66612-11-1); HC Yellow No. 9 (Cas-No.:86419-69-4); HC Yellow No. 10 (Cas-No.: 109023-83-8); HC Yellow No. 11(Cas-no.: 73388-54-2); HC Yellow No. 12 (Cas-No.: 59320-13-7); HC YellowNo. 13 (Cas-No.: 10442-83-8); the compound of formula

HC compound of formula

the compound of formula

HC Brown No. 1 (Cas-No.: 83803-98-9); HC Brown No. 2 (Cas-No.:83803-99-0); HC Green No. 1 (Cas-No.: 52136-25-1).

The nanodispersions used according to this invention can have thefollowing functions:

-   -   being carriers for allowing dyes to penetrate through certain        potential walls into media such as skin, hair or nails;    -   protecting the dyes from other ingredients of a formulation (or        vice versa, protecting the formulation from another dyes), for        example in order to eliminate incompatibilities between        formulation and solid. The dye is then separated in the core of        the nanodispersion from the remainder of the formulation. Thus        it is possible to prevent chain reactions with other ingredients        which reactions are photo-initiated by the dye;    -   introducing dyes which are only soluble in oil phases into        aqueous systems and stabilising them. The dye is then dissolved        in the core of the nanodispersion (oil phase) and the        nanodispersion particle is in turn dispersed in the aqueous        phase.

In the following Examples, percentages are by weight. Unless otherwisestated, amounts of compounds used are based on the pure substance.

WORKING EXAMPLES FOR NANODISPERSION PREPHASES Example 1 Miglyol 812Nanodispersion Prephase

soybean lecithin 17.30% polysorbate 80 34.00% miglyol 812 34.50% ethanol14.20%

Preparation: Miglyol 812 and polysorbate 80 are mixed. The soybeanlecithin is dissolved in ethanol and added to this mixture, resulting ina homogeneous clear liquid.

Example 2 Miglyol 812 Nanodispersion Prephase

soybean lecithin 17.30% oleth-20 34.00% miglyol 812 34.50% ethanol14.20%

Preparation: Miglyol 812 and oleth-20 are mixed, with heating. Thesoybean lecithin is dissolved in ethanol and added to this mixture,resulting in a homogeneous clear liquid.

Example 3 Miglyol 812 Nanodispersion Prephase

soybean lecithin 17.30% laneth-20 34.00% miglyol 812 34.50% ethanol14.20%

Preparation: Miglyol 812 and Laneth-20 are mixed, with heating. Thesoybean lecithin is dissolved in ethanol and added to this mixture,resulting in a homogeneous clear liquid.

Example 4 Miglyol 812 Nanodispersion Prephase

soybean lecithin 17.30% vitamin E polyethylene glycol succinate 34.00%(vitamin E TPGS, Eastman) miglyol 812 34.50% ethanol 14.20%

Preparation: Miglyol 812 and vitamin E polyethylene glycol succinatesare mixed, with heating. The soybean lecithin is dissolved in ethanoland added to this mixture, resulting in a homogeneous clear liquid.

Example 5 Vitamin E Acetate Nanodispersion Prephase

soybean lecithin  9.00% polysorbate 80 34.00% vitamin E acetate 36.60%miglyol 812 13.00% ethanol  7.40%

Preparation: Miglyol 812, vitamin E acetate and polysorbate 80 aremixed. The soybean lecithin is dissolved in ethanol and added to thismixture, resulting in a homogeneous clear liquid.

Example 6 Parsol MCX/parsol 5000 Nanodispersion Prephase

soybean lecithin  5.00% polysorbate 80 34.00% parsol MCX 25.90% (octylmethoxycinnamate) parsol 5000 11.10% (4-methylbenzylidene camphor)miglyol 812 13.00% ethanol 11.00%

Preparation: Parsol 5000 is dissolved in Parsol MXC and mixed withmiglyol 812 and polysorbate 80. The soybean lecithin is dissolved inethanol and added to this mixture, resulting in a homogeneous clearliquid.

WORKING EXAMPLES FOR NANODISPERSION Example 7 Miglyol 812 Nanodispersion

soybean lecithin  1.73% polysorbate 80  3.40% miglyol 812  3.45% ethanol 1.42% aqua purificata ad 100.00%

Preparation: The water phase (e.g. 90 kg) is placed, with stirring (e.g.magnetic agitator), in a vessel at 50° C. The liquid nanodispersionprephase of Example 1 (e.g. 10 kg) is added to the water phase withstirring (e.g. using a magnetic agitator).

Example 8 Miglyol 812 Nanodispersion

soybean lecithin  1.73% oleth-20  3.40% miglyol 812  3.45% ethanol 1.42% aqua purificata ad 100.00%

The preparation is carried out in analogy to the procedure of Example 7.

Example 9 Migylol 812 Nanodispersion

soybean lecithin  1.73% laneth-20  3.40% miglyol 812  3.45% ethanol 1.42% aqua purificata ad 100.00%

The nanodispersion is prepared in analogy to the procedure of Example 7.

Example 10 Miglyol 812 Nanodispersion

soybean lecithin  1.73% vitamin E polyethylene glycol succinate  3.40%(vitamin E TPGS, Eastman) miglyol 812  3.45% ethanol  1.42% aquapurificata ad 100.00%

The nanodispersion is prepared in analogy to the procedure of Example 7.

Example 11 Dexpanthenol Nanodispersion

dexpanthenol 5.00% soybean lecithin 1.73% polysorbate 80 3.40% miglyol812 3.45% ethanol 1.42% aqua purificata ad 100.00%

Preparation: The water phase containing dexpanthenol (e.g. 90 kg) isplaced, with stirring (e.g. magnetic agitator), at 50° C. in a vessel.The liquid nanodispersion prephase of Example 1 (e.g. 10 kg) is added tothe water phase with stirring (e.g. by means of a magnetic agitator).

Example 12 Vitamin E Acetate Nanodispersion

vitamin E acetate 2.00% soybean lecithin 0.49% polysorbate 80 1.86%miglyol 812 0.71% ethanol 0.63% aqua purificata ad 100.00%

Preparation: The water phase (e.g. 94.54 kg) is placed, with stirring(e.g. magnetic agitator), at 50° C. in a vessel. The liquidnanodispersion prephase of Example 5 (e.g. 5.46 kg) is added to thewater phase with stirring (e.g. by means of a magnetic agitator).

Example 13 Parsol MCX/parsol 5000 Nanodispersion

parsol MCX 2.59% (octyl methoxycinnamate) Parsol 5000 1.11%(4-methylbenzylidene camphor) miglyol 812 1.30% soybean lecithin 0.50%polysorbate 80 3.40% ethanol 1.10% aqua purificata ad 100.00%

The nanodispersion is prepared in analogy to the procedure or Example 7.

Particle sizes and particles size distribution are compiled in thefollowing Table.

TABLE 1 Particle Standard Particle diameter¹ deviation sizeNanodispersion [nm] [nm] distribution migylol 812 nanodispersion 13.84.1 Gauss Example 7 dexpanthenol nanodispersion 19.7 5.4 Gauss Example11 vitamin E acetate nanodispersion 12.2 5.5 Gauss Example 12 parsolMCX/parsol 5000 14.6 5.2 Gauss nanodispersion Example 13 ¹The particlesize diameters and particle size distributions are determined via laserlight scattering (Nicomp 370 Submicron Particle Sizer, numberweighting).

As the following Tables show, the nanodispersions also have excellentstorage stability:

Dexpanthenol Nanodispersion (Example 11)

TABLE 2 Storage conditions Standard Duration Temperature Diameter²deviation Dexpanthenol³ [months] [° C.] pH [nm] [nm] content [%] 0 6.119.7 5.4 5.37 3  7 6.1 19.0 6.7 5.36 25 6.1 22.2 7.7 5.32 40 6.3 36.614.2 5.23 6  7 6.1 20.8 7.3 5.30 25 6.2 24.1 9.2 5.26 40 6.4 35.4 17.75.20 ²The particle diameters and particle size distribution aredetermined via laser light scattering (Nicomp 370 Submicron ParticleSizer, volume weighting) ³The dexpanthenol content is determined viaHPLCVitamin E Acetate Nanodispersion (Example 12)

TABLE 3 Storage conditions Standard Vitamin E Duration TemperatureDiameter⁴ deviation acetate content [months] [° C.] pH [nm] [%] [%]⁵ 06.1 12.2 5.5 2.04 3  7 6.1 16.1 6.6 2.02 25 6.1 17.5 7.0 2.04 40 6.015.4 6.8 2.01 6  7 6.1 17.0 6.9 2.04 25 6.0 17.6 7.2 2.03 40 6.0 20.87.9 2.02 ⁴The particle diameters and particle size distributions aredetermined via laser light scattering (Nicomp 370 Submicron ParticleSizer, volume weighting) ⁵The vitamin E acetate content is determinedvia HPLC

WORKING EXAMPLE FOR COSMETIC END FORMULATIONS WITH NANODISPERSIONSExample 14 O/W Treatment Lotion

polyglycerol methyl glucose distearate 2.00% capric/capryl triglyceride6.50% mineral oil 6.50% glycerol 3.00% nanodispersion of Example 125.00% carbomer 0.20% alcohol 10.00% phenoxyethanol + methyl-, ethyl-,propyl-, butylparabene 0.30% perfume 0.30% sodium hydroxide (45%) 0.09%water ad 100.00%

Example 15 Day Cream with UV Protection (O/W)

PEG-5 glycerol stearate 5.0% steareth-21 2.0% mineral oil 30.0% cetylalcohol 2.0% microcrystalline wax 1.0% propylene glycol 6.0%nanodispersion of Example 13 10.0% phenoxyethanol + methyl-, ethyl-,propyl-, butylparabene 0.3% water ad 100.0%

Example 16 Liquid Syndet Having Fat-Restoring Properties

fatty alcohol ether sulfate 7.5% fat restoring agent 3.0% pearl lustre2.0% thickener 1.0% nanodispersion of Example 10 5.0% perfume 0.3% waterad 100.0%

Example 17 Foam Bath Having Treatment Properties

sodium lauryl ether sulfate 9.0% coconut fatty acid diethanolamide 2.0%polyglycol fatty acid ester (3EO) 3.0% perfume 1.0% nanodispersion ofExample 7 4.0% preservative, citric acid, sodium chloride, water ad100.0%

Example 18 Soothing O/W Lotion

stearic acid 1.50% sorbitan monostearate 1.00% sorbitan monooleate 1.00%mineral oil 7.00% cetyl palmitate 1.00% polymethylsiloxane 1.50%glycerol 2.00% 1.2-propylene glycol 2.00% nanodispersion of Example 113.00% polyacrylic acid 0.15% sodium hydroxide 0.30% perfume 0.50%preservative, water ad 100.00%

Example 19 Skin Protecting W/O Lotion

glycerol sorbitan fatty acid ester 2.0% polyethoxy fatty acid ester 2.0%isopropylisostearate 5.0% mineral oil 7.0% isopropylpalmitate 4.0% wheatgerm oil 3.0% propylene glycol 3.8% nanodispersion of Example 12 5.0%MgSO₄ x 7H2O 0.7% perfume 0.5% perservative, water ad 100.0%

Example 20 Make-Up Cream

glycerol monostearate 4.0% cetyl alcohol 1.0% stearic acid 2.0% mineraloil 4.5% cetylstearyloctanoate 5.0% octylpalmitate 3.0% talcum 4.0%titanium dioxide 1.5% iron oxide 0.8% propylene glycol 5.0%polyethoxysorbitan monolaurate 1.0% xanthane 0.4%magnesium-aluminium-silicate 0.3% glycerol 5.0% nanodispersion ofExample 13 5.0% preservative, water ad 100.0%

Example 21 Dexpanthenol Controlled Dosage Spray

phenoxyethanol 0.5% nanodispersion of Example 11 ad 100.0%

1. A method of preparing a cosmetic formulation of a lipophilic cosmeticactive agent in the form of an aqueous nanodispersion, which stepsconsist essentially of (α) mixing the components (a) 0.1 to 30% byweight of a phospholipid, (b) 1 to 50% by weight of a polyoxyethylenecoemulsifier selected from the group consisting of polyethoxylated fattyalcohols, polyethoxylated fatty acids, polyethoxylated vitamin Ederivatives, polyethoxylated lanolin and derivatives thereof,polyethoxylated fatty acid partial glycerides, polyethoxylatedalkylphenols, polyethoxylated fatty alcohols and salts thereof,polyethoxylated fatty amines and fatty acid amides and polyethoxylatedcarbohydrates, (c) 0.1 to 80% by weight of a lipophilic component whichis a natural or synthetic or a partially synthetic C₄-C₁₈triglycerideand a lipophilic cosmetically active agent, in which any cosmeticallyactive agent is lipophilic and is always present in component (c), and(d) 7.40 to 14.2% by weight of ethanol, with conventional stirringapparatus until a homogeneous clear liquid is obtained, and (β) addingthe liquid obtained in step (α) to a water phase, wherein step (β) iscarried out in the absence of high shear or cavitation forces, andwherein the particles in the nanodispersion have an average diameter of<50 nm.
 2. A method according to claim 1, wherein step (α) is carriedout in an anhydrous medium.
 3. A method according to claim 1, whereinthe nanodispersion comprises as component (c) a sunscreen or afat-soluble vitamin.
 4. A method according to claim 1, wherein thenanodispersion is present in the cosmetic formulation in a concentrationof 0.01 to 99% by weight.
 5. A cosmetic formulation in the form of a gelhaving incorporated therein a nanodispersion as defined in claim 1comprising a lipophilic cosmetic active agent.
 6. A cosmetic formulationin the form of a cream, lotion or milk having incorporated therein ananodispersion as defined in claim 1 comprising a lipophilic cosmeticactive agent.
 7. A cosmetic formulation in the form of a stick havingincorporated therein a nanodispersion as defined in claim 1 comprising alipophilic cosmetic active agent.
 8. A cosmetic formulation in the formof a spray or aerosol having incorporated therein a nanodispersion asdefined in claim 1 comprising a lipophilic cosmetic active agent.
 9. Acosmetic formulation in the form of a foam having incorporated therein ananodispersion as defined in claim 1 comprising a lipophilic cosmeticactive agent.
 10. A cosmetic formulation in the form of a paste havingincorporated therein a nanodispersion as defined in claim 1 comprising alipophilic cosmetic active agent.
 11. A cosmetic formulation in the formof a powder, lacquer, pellet or cosmetic make-up having incorporatedtherein a nanodispersion as defined in claim 1 comprising a lipophiliccosmetic active agent in which the nanodispersion is present indehydrated form.